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Hypomethylation of repetitive elements in blood leukocyte DNA and risk of gastric lesions in a Chinese population
Institution:1. Department of Public Health, Graduate School, Yonsei University, Seoul 120-752, Republic of Korea;2. Department of Emergency Medicine, Myongi Hospital, Goyang-si, Republic of Korea;3. National Health Insurance Service, Republic of Korea;4. Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul 120-752, Republic of Korea;1. Mallorca Cancer Registry, Spain;2. University of the Balearic Islands, Spain;3. Unit of Research, Mallorca Department of Primary Health Care, Spain;1. Population Health Department, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, Australia;2. Institute of Cancer Epidemiology, University of Lübeck, Lübeck, Germany;3. School of Population Health, University of Queensland, Herston, Australia;4. Cancer Research UK Manchester Institute and University of Manchester, Manchester Academic Health Sciences Centre, Manchester, UK;1. Catalan Institute of Oncology—Plan for Oncology of the Catalan Government, IDIBELL, Av Gran Via 199-203, 08908 Hospitalet de Llobregat, Catalonia, Spain;2. Department of Clinical Sciences, University of Barcelona, Barcelona 08907, Spain;3. Biomedical Research Institute (IdIBGi), Girona 17005, Spain;4. Computer Science, Applied Mathematics and Statistics Department of the University of Girona (UdG), Girona 17041, Spain;5. Servicio de Investigación y Análisis IT-EP, MC Mutual, Carrer de Provença, 344, Barcelona 08037, Spain;6. European Commission, DG Joint Research Centre, Institute for Health and Consumer Protection, Public Health—Cancer Policy Support, 21020 Ispra (Varese), Italy;1. Surveillance and Health Services Research, American Cancer Society, Atlanta, United States;2. Department of Epidemiology, Tata Memorial Hospital, Parel, Mumbai, India;3. Department of Digestive Diseases, Tata Medical Center, Kolkata, India;1. Group Infection and Cancer, School of Medicine and Corporación Académica para el Estudio de Patologías Tropicales, Universidad de Antioquia (UdeA), Medellín, Colombia;2. Registro Poblacional de Cancer de Cali, Universidad del Valle, Cali, Colombia;3. Grupo Epidemiologia, Instituto Nacional de Cancerologia, Bogotá, Colombia;4. IDIBELL, Institut Català d''Oncologia—Catalan Institute of Oncology, L''Hospitalet de Llobregat, Barcelona, Spain;5. CIBER en Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
Abstract:BackgroundTo explore the association between hypomethylation of repetitive elements (LINE-1, Sat2, and ALU) in blood leukocyte DNA and risks of gastric lesions, and development of gastric cancer (GC), a population-based study was conducted in a high-risk area of GC in China.MaterialsMethylation levels were determined by MethyLight in 902 subjects with various gastric lesions from two cohort studies at baseline and 276 subjects with long-term follow-up data.ResultsThe frequency of LINE-1 or Sat2 hypomethylation was significantly increased in subjects with dysplasia (DYS) compared with superficial gastritis/chronic atrophic gastritis. The odds ratios (ORs) were 2.22 95% confidence interval (CI): 1.45–3.40] for LINE-1 and 1.58 (95% CI: 1.14–2.21) for Sat2. A dose–response pattern was found for the risk of DYS and LINE-1 hypomethylation (P-trend < 0.001). Further stratified analysis indicated that the frequency of LINE-1 or Sat2 hypomethylation was higher in subjects with Helicobacter pylori infection. The ORs were 1.83 (95% CI: 1.12–2.99) for LINE-1 and 1.44 (95% CI: 1.01–2.05) for Sat2. The follow-up data indicated that the risk of progression to GC was increased in intestinal metaplasia (IM) subjects with LINE-1 hypomethylation (OR = 2.82; 95% CI: 1.17–6.77) or Sat2 hypomethylation (OR = 2.78; 95% CI: 1.15–6.74). The risk of progression to GC was also increased in DYS subjects with Sat2 hypomethylation (OR = 5.24; 95% CI: 2.00–13.74).ConclusionsThese findings suggest that hypomethylation of repetitive elements in blood leukocytes is associated with the risks of advanced gastric lesions and development of GC.
Keywords:Methylation  Repetitive elements  Gastric lesions
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